The Clinical Value Of Fecal Calprotectin Level In The Early Diagnosis Of Necrotizing Enterocolitis In Preterm Infants

Background: Necrotizing enterocolitis(NEC)is a severe gastrointestinal disorder in preterm infants.The initial clinical manifestations of NEC are nonspecific and indistinguishable from other gastrointestinal disorders and sepsis.Diagnosis is further hampered by limited diagnostic accuracy of laboratory tests and currently used imaging modalities,especially in the early detection of intestinal necrosis that required surgical treatment.Finding a reliable,specific and sensitive biomarker for early diagnosis,which could provide early diagnosis and intervention for infants with NEC,prevent other infants without NEC from receiving unnecessary treatment and prolonged cessation of enteral feedings.Fecal calprotectin(FC)is an intestinal inflammatory markers,and the level of which is correlated with the severity of intestinal inflammatory and gradually decline with the treatment.Fecal calprotectin is expected to become an useful and noninvasive biomarkers for early diagnosis and determination of the severity of NEC,also to monitor the response to NEC treatment.Objective:To explore the clinical value of fecal calprotectin level for the early diagnosis,severity prediction and therapeutic effect of necrotizing enterocolitis in preterm infants.Materials and methods:This study was conducted between January 1,2015 to January 31,2016.76 premature infants suspected of NEC were recruited as the observation group,who were hospitalized in Department of Neonatology,Teaching Hospital of Fujian Medical University,Fujian Maternity and Childern Hospital.According to the final diagnosis of the Modified Bell's stages,this group was divided into case group and feeding intolerance group.The Modified Bell's stages were stage I(n=15),II(n=15)and III(n=15)in the case group of NEC.Meanwhile,38 premature infants without feeding intolerance,who were gestational age,birth weight and gender matched were assigned to the control group.Infants with congenital digestive system malformations,inherited metabolic diseases and chromosomal defects were excluded.In the case group and the intolerance group,we collected samples at the early symptoms and signs of NEC within 24 hours and 48 hours,and the recovery phase,respectively.While,in the control group collection of the samples was adjusted according to the postnatal age of the premature infants with NEC.Finally,by using enzyme linked immunosorbent assay(ELISA)to compare FC level of each groups,which contribute to calculate sensitivity and specificity for the diagnosis of NEC.Receiver operating characteristics(ROC)curves were drawn to determine the cutoff levels of FC in diagnosis of NEC.Results:1.The median concentrations of FC at the early symptoms and signs suspected of NEC with in 24 hours(FC1)were 101.62pg/ml(74.56-158.71),54.78pg/ml(45.90-65.72)in case group and feeding intolerance group,respectively,while within 48 hours(FC2)were 95.57pg/ml(71.57-175.46),52.13pg/ml(43.45-65.46),respectively,and all were significantly higher than those of the control group 37.88pg/ml(28.81-43.78).(P=0.000).2.The median concentrations of FC when disease recovered(FC3)were 38.45pg/ml(31.46-49.76),41.45pg/ml(31.14-48.74),in case group and feeding intolerance group,respectively.There is no significantly difference between this two groups(P=0.221).However,it showed that concentrations of FC were significantly lower in the time of disease recovered than those in the early stage of disease.(P<0.05)3.The concentrations of FC1 were used for drawing ROC curve.The cutoff value,sensitivity and specificity of FC in the diagnosis of NEC were 57.95pg/ml,89.47%,78.95%,respectively.The correct diagnosis index,positive likelihood ratio and negative likelihood ratio were 68.41%,4.25,0.15,respectively.4.The median concentrations of FC1 were 68.88pg/ml(54.37-80.16),122.54pg/ml(96.78-141.16),194.60pg/ml(158.71-310.95)in stage I,stage II and stage III of NEC respectively.The median concentrations of FC2 were 69.13pg/ml(56.11-80.92),146.51pg/ml(113.68-176.76),267.79pg/ml(174.46-388.57)in stage I,stage II and stage III of NEC respectively.The median concentrations of FC3 were 38.45pg/ml(31.46-49.76),41.45pg/ml(31.14-48.74),39.49pg/ml(34.07-44.53)in stage I,stage II and stage III of NEC respectively.The concentrations of FC1 and FC2 were significantly different among the three groups,P=0.000,while three were not significantly different in FC3,P=0.308.Spearman rank correlation analysis were used between the concentrations of FC and the stage of NEC,the correlation coefficient is0.722,P value is : 0.000.Conclusions:The concentrations of FC rised at the early stage of NEC,and could be one of the useful noninvasive biomarker for early diagnosis and severity prediction of NEC.